Early micro- and macro-angiopathy in the streptozotocin diabetic minipig

Marshall, M.; Oberhofer, H.; Staubesand, J.

doi:10.1007/bf01851843

Cited by 18 publications

(19 citation statements)

References 21 publications

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“…We documented that mean fasting plasma insulin concentrations were similar in 130 mg/kg STZ-diabetic pigs (mean, 9 mU/L; range, 1-38 mU/L) compared with normal pigs (mean, 5 mU/L; range, 2-10 mU/L). Normal fasting plasma insulin concentrations have been observed before in alloxandiabetic minipigs [47], but the studies with STZ-diabetic (mini)pigs showed fasting hypoinsulinemia [6][7][8]25,26,48]. As discussed previously [48], the discrepancy in fasting plasma insulin concentrations may be explained by different strain, age, and sex, but also by different betacell toxic compound (alloxan or STZ) and the way of STZ administration.…”

Section: Discussionmentioning

confidence: 90%

“…Because lipoprotein and lipid metabolism in humans and pigs are very alike [3,4], it may be expected that streptozotocin (STZ) treatment for pigs (ie, the chemical induction of diabetes) can create a type 2-like diabetic pig model with regard to insulin resistance, glucose homeostasis, dyslipidemia, and the response to oral anti-type 2 diabetes mellitus drug therapy. Streptozotocin, a chemical agent that damages pancreatic beta cells, has frequently been used to induce insulin-deficient diabetes in many species [22][23][24][25], and depending on the dose and strategy of STZ administration, a type 1-like [7,26,27], or a type 2-like [28][29][30][31], diabetes mellitus can be generated. Rapid intravenous injection of STZ at doses of around 100 mg/kg or higher produces insulin-dependent diabetes in pigs within days after STZ administration, and diabetes remains present for periods up to 3 years [6,7,25,26].…”

Section: Introductionmentioning

confidence: 99%

“…Streptozotocin, a chemical agent that damages pancreatic beta cells, has frequently been used to induce insulin-deficient diabetes in many species [22][23][24][25], and depending on the dose and strategy of STZ administration, a type 1-like [7,26,27], or a type 2-like [28][29][30][31], diabetes mellitus can be generated. Rapid intravenous injection of STZ at doses of around 100 mg/kg or higher produces insulin-dependent diabetes in pigs within days after STZ administration, and diabetes remains present for periods up to 3 years [6,7,25,26]. Lower doses of STZ result, in general, in a transient or absent diabetic reaction in pigs [6,32].…”

Section: Introductionmentioning

confidence: 99%

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Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs

et al. 2006

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs

et al. 2006

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“…Substantially increased fasting plasma glucose (FPG) levels and decreased insulin secretion in response to glucose stimuli have been obtained as well as increases in plasma triglycerides and total cholesterol (27,29). Late complications typical of diabetes, such as capillary basement membrane thickening and cataracts, have also been shown in diabetic minipigs (28,41).In other studies, alloxan has been used for induction of diabetes in pigs (11,25,41). This compound, which has ␤-cell-toxic properties similar to those of STZ, in a dose of 200 mg/kg in Yucatan minipigs induced severe diabetes with high mortality due to hypoglycemia following acute hyperinsulinemia as a consequence of massive ␤-cell damage (41).…”

mentioning

confidence: 91%

Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes

Larsen

Wilken

Gotfredsen

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

113

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Intermediate NIA doses induced moderate changes of glucose tolerance [glucose area under the curve increased from 940 Ϯ 175 to 1,598 Ϯ 462 mM ⅐ min, P Ͻ 0.001 (100 mg/kg) and from 890 Ϯ 109 to 1,669 Ϯ 691 mM ⅐ min, P ϭ 0.003 (67 mg/kg)] with reduced insulin secretion [1,248 Ϯ 602 pM ⅐ min after 16 days and 1,566 Ϯ 190 pM ⅐ min after 60 days vs. 3,251 Ϯ 804 pM ⅐ min in normal animals (P Ͻ 0.001)] and ␤-cell mass [5.5 Ϯ 1.4 mg/kg after 27 days and 7.9 Ϯ 4.1 mg/kg after 60 days vs. 17.7 Ϯ 4.7 mg/kg in normal animals (P ϭ 0.009)]. The combination of NIA and STZ provided a model characterized by fasting and especially postprandial hyperglycemia and reduced, but maintained, insulin secretion and ␤-cell mass. This model holds promise as an important tool for studying the pathophysiology of diabetes and development of new pharmacological agents for treatment of the disease.in vivo pharmacology; large-animal model; glucose tolerance; ␤-cell reduction; glucose-stimulated insulin secretion.THE STUDY OF THE PATHOPHYSIOLOGY and treatment of diabetes requires well characterized animal models that resemble aspects of the disease in humans. Various forms of diabetes occur spontaneously or can be induced in several species of animals. Most of the available models are based on rodents; however, nonrodent models of diabetes are urgently needed as a valuable supplement to rodents for both practical and physiological reasons.The pig is useful as a model for human physiology and pathophysiology, because many organ systems resemble those of the human. Of special interest for the study of diabetes is the similarities to humans found in the clinical chemistry (7,10,12,14,24,26,55), nutrition and gastrointestinal tract (4,8,11,20,35,40,51), pancreas development and morphology (21,36,37,44,49,54), and metabolism (3, 35). These characteristics make swine an interesting species for studies of metabolic abnormalities in diabetes. The Göttingen minipig is especially suitable for long-term studies because of its small size and ease of handling, even at full maturity (6).Pancreatectomy has been investigated as a method of inducing diabetes in pigs (33,34,50,55). However, high rates of mortality have been observed postoperatively (50, 55), meaning that this technique should be used with great caution, and alternatives should be considered because of welfare considerations. Chemical induction of diabetes offers the advantage of preservation of both exocrine and endocrine cell populations other than ␤-cells, thus resembling the situation in human diabetes (55). Several stable models have been established for overt type 1 diabetes in the pig by the use of pharmacological induction of ␤-cell damage with streptozotocin (STZ), either as single or repeated injections (2, 15, 16, 27-29, 46, 55). Substantially increased fasting plasma glucose (FPG) levels and decreased insulin secretion in response to glucose stimuli have been obtained as well as increases in plasma triglycerides and total cholesterol (27,29). Late complications typical of diabetes, such...

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“…Due to the anatomical, physiological, and metabolic similarities with human body, mini-pigs are considered as a suitable model in biomedical research. 24 The common blood biochemical index of mini-pigs and the absorption, transfer, and utilization of glucose are also similar to the corresponding processes in humans. 25 Thus, mini-pigs can be considered a valuable model for observing bone remodeling and the interaction between bone and implants under the impact of diabetes.…”

mentioning

confidence: 81%

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs

Tan

Liu

Cai

et al. 2017

IJN

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Background High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models. Methods Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO). A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg), and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT) and histologic evaluations were performed 3 and 6 months after implantation. Results The Ra (the average of the absolute height of all points) of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months, although this difference disappeared by 6 months. DLMS implants showed a higher bone–implant contact percentage (33.2%±11.2%) at 3 months compared with MAO group (18.9%±7.3%) while similar results were showed at 6 months between DLMS group (42.8%±10.1%) and MAO group (38.3%±10.8%). Conclusion The three-dimensional environment of implant surfaces with highly porous and fully interconnected channel and pore architectures can improve cell spreading and accelerate the progress of osseointegration in diabetic mini-pigs.

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Early micro- and macro-angiopathy in the streptozotocin diabetic minipig

Cited by 18 publications

References 21 publications

Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs

Association of insulin resistance with hyperglycemia in streptozotocin-diabetic pigs

Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs

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